1.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
2.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
3.Discordance in Claudin 18.2Expression Between Primary and Metastatic Lesions in Patients With Gastric Cancer
Seung-Myoung SON ; Chang Gok WOO ; Ok-Jun LEE ; Sun Kyung LEE ; Minkwan CHO ; Yong-Pyo LEE ; Hongsik KIM ; Hee Kyung KIM ; Yaewon YANG ; Jihyun KWON ; Ki Hyeong LEE ; Dae Hoon KIM ; Hyo Yung YUN ; Hye Sook HAN
Journal of Gastric Cancer 2025;25(2):303-317
Purpose:
Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods.
Materials and Methods:
We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features.
Results:
CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues.
Conclusions
CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.
4.Conventional machine learning-based prediction models did not outperform the International IgA Nephropathy Prediction Tool
Sehoon PARK ; Yisak KIM ; Chung Hee BAEK ; Hyunjeong CHO ; Ji In PARK ; Eun Sil KOH ; Jung Pyo LEE ; Sun-Hee PARK ; Hyung Woo KIM ; Seung Hyeok HAN ; Ho Jun CHIN ; Dong Ki KIM ; Kyung Chul MOON ; Young-Gon KIM ; Hajeong LEE
Kidney Research and Clinical Practice 2025;44(5):802-813
Immunoglobulin A nephropathy (IgAN) is a major cause of end-stage kidney disease (ESKD). The International IgA Nephropathy Prediction Tool (IIgAN-PT) predicts IgAN prognosis, but improvement in the prediction performance using machine learning (ML)-based methods is needed. Methods: We analyzed 4,425 biopsy-confirmed patients with IgAN and ≥6 months of follow-up from nine tertiary university hospitals in Korea. The study population was divided into development and validation cohorts. Using the collected 87 clinicodemographic and pathological variables, ML-based prediction models for ESKD or estimated glomerular filtration rate decline (50% reduction or <15 mL/min/1.73 m2 ) were constructed: 1) the conventional CatBoost model, 2) the optimized CatBoost model with Cox proportional hazards, 3) the deep Cox proportional hazards model, and 4) the deep Cox mixture model. The area under the curve (AUC) and calibration plots were used to investigate the discriminative and calibration performance of the models, which were then compared with those of the IIgAN-PT full model. Results: The full model showed excellent performance (AUC [95% confidence interval] for 5-year outcome, 0.896 [0.853–0.940]), with acceptable calibration results. The ML-based models showed good performance in predicting adverse kidney outcomes and revealed acceptable discrimination performance in the external validation (AUC [95% confidence interval] for the 5-year outcome: 1) 0.829 [0.791–0.866]; 2) 0.847 [0.804–0.890]; 3) 0.823 [0.784–0.862]; and 4) 0.832 [0.794–0.870]), although the models showed underestimation in calibration analysis of the external validation cohort. With the validation data, the overall performance of the IIgAN-PT was non-inferior to that of the ML-based model. Conclusions: Our ML-based models showed good performance in predicting adverse kidney outcomes in patients with IgAN but they did not outperform the IIgAN-PT.
5.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
6.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
7.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
8.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
9.Association Between Oral Health and Gastric Cancer in Korean Adults
Sang Hoon LEE ; Hyunseok CHO ; Sung Chul PARK ; Sang Hoon KIM ; Seung Young KIM ; Han Jo JEON ; Sang Pyo LEE ; Younghee CHOE ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2024;24(4):346-352
Objectives:
Poor oral hygiene is known to be associated with gastric cancer, but this remains controversial. In this study, we investigated the association between oral health and gastric cancer in Korean adults using data from the Korea National Health and Nutrition Examination Survey.
Methods:
We analyzed data of 79501 patients with gastric cancer and 41856805 individuals without gastric cancer (control group) using the 7th and 8th Korea National Health and Nutrition Examination Survey (2016–2019) records. Layer and colony variables and weights were used for the complex sample design. We performed logistic regression analysis of complex samples to analyze factors that affect gastric cancer development.
Results:
Patients with gastric cancer were older and had a higher prevalence of hypertension, hyperlipidemia, and diabetes and a higher rate of current smoking and alcohol consumption than individuals without gastric cancer (p<0.001). Regarding oral health-related factors, the prevalence of very uncomfortable chewing difficulty was significantly higher in patients with gastric cancer (14.4% vs. 3.6%, p<0.001). On multivariate analysis of factors associated with gastric cancer, chewing difficulty showed the highest odds ratio (5.351, 95% confidence interval 2.128–8.982). Patients with very uncomfortable chewing difficulty had high rates of previous dental nerve treatment, gum disease treatment, tooth extraction or intraoral surgery, and prosthetic repair (p<0.001).
Conclusions
Oral health-related chewing difficulties were associated with gastric cancer, which may be attributable to poor oral hygiene and degradation of oral microbiota. Patients at risk of gastric cancer warrant timely medical interventions to address their oral health and chewing difficulties.
10.Risk of mortality and cause of death according to kidney function parameters: a nationwide observational study in Korea
Sehyun JUNG ; Soojin LEE ; Yaerim KIM ; Semin CHO ; Hyuk HUH ; Yong Chul KIM ; Seung Seok HAN ; Hajeong LEE ; Jung Pyo LEE ; Kwon Wook JOO ; Chun Soo LIM ; Yon Su KIM ; Dong Ki KIM ; Kyungdo HAN ; Sehoon PARK
Kidney Research and Clinical Practice 2024;43(2):202-215
Further study is warranted to determine the association between estimated glomerular filtration rate (eGFR) or albuminuria and the risk of death from diverse causes. Methods: We screened >10 million general health screening examinees who received health examinations conducted in 2009 using the claims database of Korea. After the exclusion of those previously diagnosed with renal failure and those with missing data, 9,917,838 individuals with available baseline kidney function measurements were included. The primary outcome was mortality and cause-specific death between 2009 and 2019 identified through death certificates based on the diagnostic codes of International Classification of Diseases, 10th revision. Multivariable Cox regression analysis adjusted for various clinicodemographic and social characteristics was used to assess mortality risk. Results: The hazard ratio of death was significantly high in both the eGFR <60 mL/min/1.73 m2 and in the eGFR ≥120 mL/ min/1.73 m2 groups in univariable and multivariable regression analyses when compared to those within the reference range (eGFR of 90–120 mL/min/1.73 m2). The results were similar for death by cardiovascular, cancer, infection, endocrine, respiratory, and digestive causes. We also found that albuminuria was associated with higher risk of death regardless of eGFR range, and those in the higher categories of dipstick albuminuria showed higher risk. Conclusion: We reconfirmed the significant association between eGFR, albuminuria, and mortality. Healthcare providers should keep in mind that albuminuria and decreased eGFR as well as kidney hyperfiltration are independent predictors of mortality.

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